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Killer immunoglobulin like receptors

Vivien Béziat, Hugo Hilton, Paul J Norman, James A Traherne
Killer-cell immunoglobulin-like receptors (KIRs) are components of two fundamental biological systems essential for human health and survival. Firstly, they contribute to host immune response, both innate and adaptive, through their expression by natural killer (NK) cells and T cells. Secondly, KIR play a key role in regulating placentation, and hence reproductive success. Analogous to the diversity of their HLA class I ligands, KIR are extremely polymorphic. In this review, we describe recent developments, fuelled by methodological advances, which are helping to decipher the KIR system in terms of haplotypes, polymorphisms, expression patterns and their ligand interactions...
October 25, 2016: Immunology
G Kamkamidze, M Butsashvili, K Gendzekhadze
Hepatitis C virus (HCV) infection remains one of the most important blood-borne diseases worldwide with about 130-170 million people chronically infected with hepatitis C virus, and more than 350 000 people die from hepatitis C-related liver diseases each year. Infection with HCV becomes chronic in approximately 80% of cases, while in up to 20% of cases hepatitis C virus is cleared from the human organism. Chronic infections of hepatitis C often leads to the end-stage liver diseases such as cirrhosis and hepatocellular carcinoma...
September 2016: Georgian Medical News
Kate Stringaris, David Marin, A John Barrett, Robert Hills, Catherine Sobieski, Kai Cao, Jerome G Saltarrelli, May Daher, Hila Shaim, Nathaniel Smith, David Linch, Rosemary Gale, Christopher Allen, Takuya Sekine, Rohtesh Mehta, Richard Champlin, Elizabeth J Shpall, Hagop Kantarjian, Guillermo Garcia-Manero, Katayoun Rezvani
Myelodysplastic syndromes (MDS) are a group of hematopoietic disorders affecting the myeloid lineage, characterized by cytopenias and clonal evolution to acute myeloid leukemia (AML). We hypothesized that natural killer (NK) cells and their activating killer immunoglobulin-like receptors (aKIRs) influence the immune surveillance and clinical outcome of patients with MDS. Here, we first examined the distribution of aKIR genes and haplotype in two independent cohorts of MDS and AML patients. The median number of aKIR genes was lower in MDS patients than healthy controls (2 vs...
October 19, 2016: Blood
Ashley Moffett, Olympe Chazara, Francesco Colucci, Martin H Johnson
A distinctive type of (uterine) natural killer (NK) cell is present in the uterine decidua during the period of placental formation. Uterine NK cells express members of the killer immunoglobulin-like receptor (KIR) family that bind to parental HLA-C molecules on the invading placental trophoblast cells. The maternal KIR genes and their fetal ligands are highly variable, so different KIR/HLA-C genetic combinations occur in each pregnancy. Some women only possess inhibitory KIR genes, whereas other women also express activating KIR genes...
September 5, 2016: Reproductive Biomedicine Online
Farhad Shahsavar, Shaghayegh Mapar, Seyyed Amir Yasin Ahmadi
Multiple sclerosis (MS) is a disease in which we can recognize destruction of the myelin that is around nerve cells of brain and spinal cord called as oligodendrocytes. Both genetic and environmental factors play roles in MS. One of these genes is the killer-cell immunoglobulin-like receptor (KIR) which expressed on surface of natural killer cells (NKs). These genes have loci (not locus) in human genome, so they inherit as haplotypes. The results of previous studies show that different genes of KIR may affect both susceptibility and resistance to such autoimmune disorders that their pathogenesis in MS is still unclear...
December 2016: Genomics Data
Gamze Isitman, Alexandra Tremblay-McLean, Irene Lisovsky, Julie Bruneau, Bertrand Lebouché, Jean-Pierre Routy, Nicole F Bernard
Natural Killer (NK) cell education, which requires the engagement of inhibitory NK cell receptors (iNKRs) by their ligands, is important for generating self-tolerant functional NK cells. While the potency of NK cell education is directly related to their functional potential upon stimulation with HLA null cells, the influence of NK cell education on the potency of the antibody dependent cellular cytotoxicity (ADCC) function of NK cells is unclear. ADCC occurs when the Fc portion of an immunoglobulin G antibody bridges the CD16 Fc receptor on NK cells and antigen on target cells, resulting in NK cell activation, cytotoxic granule release, and target cell lysis...
2016: PloS One
Cynthia Vierra-Green, David Roe, Jyothi Jayaraman, John Trowsdale, James Traherne, Rui Kuang, Stephen Spellman, Martin Maiers
The killer cell immunoglobulin-like receptors (KIR) mediate human natural killer (NK) cell cytotoxicity via activating or inhibiting signals. Although informative and functional haplotype patterns have been reported, most genotyping has been performed at resolutions that are structurally ambiguous. In order to leverage structural information given low-resolution genotypes, we performed experiments to quantify the effects of population variations, reference haplotypes, and genotyping resolutions on population-level haplotype frequency estimations as well as predictions of individual haplotypes...
2016: PloS One
Daniele Kazue Sugioka, Carlos Eduardo Ibaldo Gonçalves, Maria da Graça Bicalho
BACKGROUND: Since the discovery of specific histocompatibility, literature has associated genes involved in the immune response, like the Human Leucocyte Antigen (HLA), with a better prognosis in transplantation. However, other non-HLA genes may also influence the immune process, such as the genes encoding the immunoglobulin-like receptors of natural killer cells (KIRs). The discovery that NK cell KIR receptors interact with conservative epitopes (C1, C2, Bw4) presented in HLA class I molecules that are genetically polymorphic, also observed in KIR genes, led to the investigation of the relevance of the KIR system to hematopoietic stem cell transplant...
2016: BMC Hematology
B Erer, M Takeuchi, D Ustek, I Tugal-Tutkun, E Seyahi, Y Özyazgan, J Duymaz-Tozkir, A Gül, D L Kastner, E F Remmers, M J Ombrello
The Behçet's disease (BD)-associated human leukocyte antigen (HLA) allele, HLA-B*51 (B*51), encodes a ligand for a pair of allelic killer immunoglobulin-like receptors (KIR) present on cytotoxic cells-KIR3DL1, which inhibits their cytotoxicity, and KIR3DS1, which activates their cytotoxic activity. We tested whether KIR-regulated mechanisms contribute to BD by testing for association of KIR3DL1/KIR3DS1 genotypes with disease in 1799 BD patients and 1710 healthy controls from Turkey, as well as in different subsets of individuals with HLA-type-defined ligands for the KIR3D receptors...
October 6, 2016: Genes and Immunity
Wei Wang, Amy K Erbe, Mikayla Gallenberger, KyungMann Kim, Lakeesha Carmichael, Dustin Hess, Eneida A Mendonca, Yiqiang Song, Jacquelyn A Hank, Su-Chun Cheng, Sabina Signoretti, Michael Atkins, Alexander Carlson, Jonathan M Weiss, James Mier, David Panka, David F McDermott, Paul M Sondel
NK cells play a role in many cancer immunotherapies. NK cell activity is tightly regulated by killer immunoglobulin-like receptor (KIR) and KIR-ligand interactions. Inhibitory KIR-ligands have been identified as HLA molecules, while activating KIR-ligands are largely unknown. Individuals that have not inherited the corresponding KIR-ligand for at least one inhibitory KIR gene are termed the "KIR-ligand missing" genotype, and they are thought to have a subset of NK cells that express inhibitory KIRs for which the corresponding KIR-ligand is missing on autologous tissue, and thus will not be inhibited through KIR-ligand recognition...
September 30, 2016: Cancer Immunology, Immunotherapy: CII
W Jiang, C Johnson, N Simecek, M R López-Álvarez, D Di, J Trowsdale, J A Traherne
Killer cell immunoglobulin-like receptors (KIRs), expressed on natural killer cells and T cells, have considerable biomedical relevance playing significant roles in immunity, pregnancy and transplantation. The KIR locus is one of the most complex and polymorphic regions of the human genome. Extensive sequence homology and copy number variation makes KIRs technically laborious and expensive to type. To aid the investigation of KIRs in human disease we developed a high-throughput, multiplex real-time polymerase chain reaction method to determine gene copy number for each KIR locus...
September 29, 2016: Genome Medicine
Hisham A Edinur, Siti M Manaf, Nor F Che Mat
The successful of transplantation is determined by the shared human leukocyte antigens (HLAs) and ABO blood group antigens between donor and recipient. In recent years, killer cell receptor [i.e., killer cell immunoglobulin-like receptor (KIR)] and major histocompatibility complex (MHC) class I chain-related gene molecule (i.e., MICA) were also reported as important determinants of transplant compatibility. At present, several different genotyping techniques (e.g., sequence specific primer and sequence based typing) can be used to characterize blood group, HLA, MICA and KIR and loci...
September 24, 2016: World Journal of Transplantation
Yuge Wang, Tracy Hwangpo, Maureen P Martin, Nicolas Vince, Ying Qi, Richard J Reynolds, Devin Absher, Xiaojiang Gao, Carol A Ballinger, Peter D Burrows, T Prescott Atkinson, Elizabeth E Brown, Ada Elgavish, Cunren Liu, Mary Carrington, Harry W Schroeder
No abstract text is available yet for this article.
September 21, 2016: Journal of Allergy and Clinical Immunology
Suliman Y Alomar, Afrah Alkhuriji, Paul Trayhyrn, Abdulkarim Alhetheel, Abdullah Al-Jurayyan, Lamjed Mansour
Breast cancer (BC) progression and metastases have been linked to antitumor immunity inefficiency and particularly to natural killer (NK) cells. Killer cell immunoglobulin-like receptors (KIRs) are the most polymorphic receptors of NK cells. Through their interactions with human leukocyte antigen (HLA)-C ligands, they modulate NK and T cell actions against target cells. Therefore, we studied the combinatorial effect of KIR genes and their HLA-C ligands on the susceptibility to development of BC in Saudi women...
September 15, 2016: Immunogenetics
Marion Depla, Sandy Pelletier, Nathalie Bédard, Camille Brunaud, Julie Bruneau, Naglaa H Shoukry
INTRODUCTION: Polymorphisms in the type III interferon IFN-λ3 and the killer cell immunoglobulin-like receptor (KIR) genes controlling the activity of natural killer (NK) cells can predict spontaneous resolution of acute hepatitis C virus (HCV) infection. We hypothesized that IFN-λ3 polymorphism may modulate NK cell function during acute HCV. METHODS: We monitored the plasma levels of type III IFNs in relation to the phenotype and the function of NK cells in a cohort of people who inject drugs (PWID) during acute HCV infection with different outcomes...
September 2016: Immunity, Inflammation and Disease
Camilla Stephens, Antonia Moreno-Casares, Miguel-Ángel López-Nevot, Miren García-Cortés, Inmaculada Medina-Cáliz, Hacibe Hallal, German Soriano, Eva Roman, Francisco Ruiz-Cabello, Manuel Romero-Gomez, M Isabel Lucena, Raúl J Andrade
Natural killer cells are an integral part of the immune system and represent a large proportion of the lymphocyte population in the liver. The activity of these cells is regulated by various cell surface receptors, such as killer Ig-like receptors (KIR) that bind to human leukocyte antigen (HLA) class I ligands on the target cell. The composition of KIR receptors has been suggested to influence the development of specific diseases, in particularly autoimmune diseases, cancer and reproductive diseases. The role played in idiosyncratic drug-induced liver injury (DILI) is currently unknown...
2016: Frontiers in Pharmacology
Amandine Pradier, Federico Simonetta, Sophie Waldvogel, Carine Bosshard, Jean-Marie Tiercy, Eddy Roosnek
Peripheral natural killer (NK) cells upregulate T-bet and downregulate Eomes, the key transcription factors regulating NK cell maturation and function during the last maturation steps toward terminally differentiated effector cells. During this process, NK cells acquire killer immunoglobulin-like receptors (KIR) and effector functions, such as cytotoxicity and target cell-induced cytokine production. Inhibitory KIR are pivotal in the control of effector functions, but whether they also modulate T-bet/Eomes expression is unknown...
2016: Frontiers in Immunology
Lutz Walter, Beatrix Petersen
The killer immunoglobulin-like receptors (KIR) as well as their MHC class I ligands display enormous genetic diversity and polymorphism in macaque species. Signals resulting from interaction between KIR or CD94/NKG2 receptors and their cognate MHC class I proteins essentially regulate the activity of natural killer (NK) cells. Macaque and human KIR share many features, such as clonal expression patterns, gene copy number variations, specificity for particular MHC class I allotypes, or epistasis between KIR and MHC class I genes that influence susceptibility and resistance to immunodeficiency virus infection...
August 27, 2016: Immunology
Kim L Weisgrau, Moritz Ries, Nicholas Pomplun, David T Evans, Eva G Rakasz
This panel was developed to measure the functional capability of natural killer (NK) cell subsets in rhesus macaques (Macaca mulatta). It includes markers to determine the frequency of cytokine secreting and cytotoxic NK cell subpopulations in peripheral blood mononuclear cell (PBMC) samples stimulated in vitro with human 721.221 cells. NK cell subsets were defined by the expression of killer cell immunoglobulin-like receptors (KIRs) Mamu-KIR3DL01 and Mamu-KIR3DL05, and differentiation antigens CD16 and CD56...
September 2016: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
Magdalena Sips, Qingquan Liu, Monia Draghi, Musie Ghebremichael, Christoph T Berger, Todd J Suscovich, Yongtao Sun, Bruce D Walker, Mary Carrington, Marcus Altfeld, Peter Brouckaert, Philip L De Jager, Galit Alter
Differences in HLA-C expression are inversely correlated with HIV viral load set-point and slower progression to AIDS, linked to enhanced cytotoxic T cell immunity. Yet, beyond T cells, HLA-C serves as a dominant ligand for Natural Killer (NK) cell Killer Immunoglobulin-like Receptors (KIR). Thus, we speculated that HLA-C expression levels may also impact NK activity, thereby modulating HIV antiviral control. Phenotypic and functional profiling was performed on freshly isolated PBMCs. HLA-C expression was linked to changes in NK subset distribution and licensing, particularly in HLA-C1/C1, KIR2DL3+2DL2- individuals...
August 10, 2016: Human Immunology
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